Paricalcitol improved cardiac hypertrophy and fibrosis through upregulation of fibroblast growth factor-23 and downregulation of transforming growth factor-beta in a rat model of isoproterenol-induced cardiomyopathy.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Chieh-Jen Wu, Yu-He Li, Hsin-Hung Chen
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引用次数: 0

Abstract

Acute cardiomyopathy is a significant global health concern and one of the leading causes of death in developed countries. Prior studies have shown an association between acute cardiomyopathy and low vitamin D levels. Although paricalcitol, a vitamin D receptor (VDR) activator, has demonstrated clinical benefits in patients with advanced kidney disease, its effect on cardiac remodeling in cardiomyopathy is unknown. This study aimed to investigate the relative effects of paricalcitol on cardiomyopathy in rats. Wistar-Kyoto rats were administered vehicle (sham control group) or isoproterenol to induce cardiomyopathy. Rats administered isoproterenol were subsequently treated with paricalcitol (experimental group) or vehicle (isoproterenol group). Picrosirius red and immunofluorescence staining were used to analyze cardiac fibrosis and hypertrophy. Immunohistochemistry staining was used to confirm the molecular mechanisms involved in isoproterenol-induced cardiomyopathy in rats. Injection of paricalcitol could reduce collagen and transforming growth factor-beta 1 (TGF-β1) levels while activating fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-23 (FGF23) without the help of Klotho, thereby reducing myocardial hypertrophy and fibrosis. As a VDR activator, paricalcitol reduces isoproterenol-induced cardiac fibrosis and hypertrophy by reducing the expression of TGF-β1 and enhancing the expression of VDR, FGFR1, and FGF23.

在异丙肾上腺素诱导的心肌病大鼠模型中,帕里骨化醇通过上调成纤维细胞生长因子-23和下调转化生长因子β来改善心肌肥大和纤维化。
急性心肌病是一个重要的全球健康问题,也是发达国家的主要死亡原因之一。先前的研究表明,急性心肌病与维生素D水平低有关。尽管维生素D受体(VDR)激活剂帕钙化醇已证明对晚期肾病患者具有临床益处,但其对心肌病心脏重塑的影响尚不清楚。本研究旨在探讨帕利骨化醇对大鼠心肌病的相关影响。Wistar Kyoto大鼠给予赋形剂(假对照组)或异丙肾上腺素以诱导心肌病。随后用帕骨化醇(实验组)或赋形剂(异丙肾上腺素组)治疗给予异丙肾上腺素的大鼠。用毕赤霉红和免疫荧光染色分析心肌纤维化和肥大。免疫组织化学染色证实了异丙肾上腺素诱导的大鼠心肌病的分子机制。在没有Klotho帮助的情况下,注射帕骨化醇可以降低胶原和转化生长因子β1(TGF-β1)水平,同时激活成纤维细胞生长因子受体1(FGFR1)和成纤维细胞增长因子-23(FGF23),从而减少心肌肥大和纤维化。作为VDR激活剂,帕钙醇通过减少TGF-β1的表达和增强VDR、FGFR1和FGF23的表达来减少异丙肾上腺素诱导的心脏纤维化和肥大。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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